Design, synthesis and in vitro evaluation of bridgehead fluoromethyl analogs of N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-N-(pyridin-2-yl) cyclohexanecarboxamide (WAY-100635) for the 5-HT1A receptor

European Journal of Medicinal Chemistry

Volumn 46, Issue 12, 2011, Pages 5728-5735

  Al Hussainy, Rana ^a   Verbeek, Joost ^a   Van Der Born, Dion ^a   Booij, Jan ^b   Herscheid, J D M ^a  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^b UNIVERSITY OF AMSTERDAM   (Netherlands)

Author keywords

5 HT1A receptor; Bridge fused ring; WAY 100635

Indexed keywords

4 (FLUOROMETHYL) N [2 [4 (2 HYDROXYPHENYL)PIPERAZIN 1 YL]ETHYL] N (PYRIDIN 2 YL)ADAMANTANE 1 CARBOXAMIDE; 4 (FLUOROMETHYL) N [2 [4 (2 HYDROXYPHENYL)PIPERAZIN 1 YL]ETHYL] N (PYRIDIN 2 YL)BICYCLO[2.2.1]HEPTANE 1 CARBOXAMIDE; 4 (FLUOROMETHYL) N [2 [4 (2 HYDROXYPHENYL)PIPERAZIN 1 YL]ETHYL] N (PYRIDIN 2 YL)BICYCLO[2.2.2]OCTANE 1 CARBOXAMIDE; 4 (FLUOROMETHYL) N [2 [4 (2 HYDROXYPHENYL)PIPERAZIN 1 YL]ETHYL] N (PYRIDIN 2 YL)CUBANE 1 CARBOXAMIDE; 4 (FLUOROMETHYL) N [2 [4 (2 METHOXYPHENYL)PIPERAZIN 1 YL]ETHYL] N (PYRIDIN 2 YL)ADAMANTANE 1 CARBOXAMIDE; 4 (FLUOROMETHYL) N [2 [4 (2 METHOXYPHENYL)PIPERAZIN 1 YL]ETHYL] N (PYRIDIN 2 YL)BICYCLO[2.2.1]HEPTANE 1 CARBOXAMIDE; 4 (FLUOROMETHYL) N [2 [4 (2 METHOXYPHENYL)PIPERAZIN 1 YL]ETHYL] N (PYRIDIN 2 YL)BICYCLO[2.2.2]OCTANE 1 CARBOXAMIDE; 4 (FLUOROMETHYL) N [2 [4 (2 METHOXYPHENYL)PIPERAZIN 1 YL]ETHYL] N (PYRIDIN 2 YL)CUBANE 1 CARBOXAMIDE; ADRENERGIC RECEPTOR; AMIDE; BRIDGED COMPOUND; DOPAMINE RECEPTOR; N [2 [4 (2 METHOXYPHENYL) 1 PIPERAZINYL]ETHYL] N (2 PYRIDYL)CYCLOHEXANECARBOXAMIDE; SEROTONIN 1A RECEPTOR; SEROTONIN ANTAGONIST; SEROTONIN RECEPTOR; SEROTONIN TRANSPORTER; SIGMA OPIATE RECEPTOR; UNCLASSIFIED DRUG;

ACYLATION; ARTICLE; BINDING AFFINITY; BROMINATION; CARBON NUCLEAR MAGNETIC RESONANCE; CHEMICAL BOND; CONTROLLED STUDY; DEFLUORINATION; DEMETHYLATION; DRUG BINDING; DRUG DECOMPOSITION; DRUG DESIGN; DRUG METABOLISM; DRUG RECEPTOR BINDING; DRUG SCREENING; DRUG SELECTIVITY; DRUG STABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; FLUORINATION; HUMAN; HUMAN CELL; HYDROLYSIS; IC 50; IN VITRO STUDY; LIPOPHILICITY; LIVER CELL; METABOLIC RATE; POSITRON EMISSION TOMOGRAPHY; PROTON NUCLEAR MAGNETIC RESONANCE;

CELL LINE; DRUG DESIGN; HALOGENATION; HUMANS; PIPERAZINES; POSITRON-EMISSION TOMOGRAPHY; PROTEIN BINDING; PYRIDINES; RECEPTOR, SEROTONIN, 5-HT1A; SEROTONIN 5-HT1 RECEPTOR ANTAGONISTS;

EID: 80955141013     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2011.06.023     Document Type: Article

References (40)

1. 4 receptor agonist Psychopharmacology 188 2006 244 251 (Pubitemid 44371162)
2. 1A) receptors in the central nervous system. Eur J. Nucl. Med. 28 2001 113 129 (Pubitemid 32120814)
3. 1A binding-sites in frontal cortex of suicide victims J. Neural Transm. 85 1991 181 194
4. V. Kepe, J.R. Barrio, S. Cheng Huang, L. Ercoli, P. Siddarth, K. Shoghi Jadid, G.M. Cole, N. Satyamurthy, J.L. Cummings, G.W. Small, and M.E. Phelps. Serotonin 1A receptors in the living brain of Alzheimer's disease patients PNAS 103 2006 702 707 (Pubitemid 43153089)
5. 1A receptors in vivo Prog. Med. Chem. 38 2001 189 247
6. 1A receptor binding in amygdala of schizophrenia Biol. Psychiatry 55 2004 439 444 (Pubitemid 38338529)
7. 11C]-WAY 100635 Med. Chem. Res. 5 1994 208 227
8. 1A receptor PET radioligands Nucl. Med. Biol. 27 2000 441 447 (Pubitemid 30658144)
9. V.W. Pike, C. Halldin, H. Wikström, S. Marchais, J.A. McCarron, J. Sandell, B. Nowicki, C.-G. Swahn, S. Osman, S.P. Hume, M. Constantinou, B. Andree, and L. Farde Radioligands for the study of brain 5-HT1A receptors in vivo-development of some new analogues of WAY Nucl. Med. Biol. 27 2000 449 455 (Pubitemid 30658145)
10. 1A ligand J. Med. Chem. 37 1994 1406 1407 (Pubitemid 24174075)
11. 1A antagonist J. Med. Chem. 42 1999 1576 1582
12. 1A antagonist for PET: an in vivo study in rat J. Neurochem. 75 2000 803 811
13. 18F]MPPF Nucl. Med. Biol. 27 2000 473 476 (Pubitemid 30658149)
14. 1A receptors in animal and human brain Neuropharmacology 52 2007 695 707 (Pubitemid 46227474)
15. 18F] labeled 3-cis-3-trans,4-cis-, and 4-trans-fluorocyclohexane derivatives of WAY 100635 Bioorg. Med. Chem. 14 2006 3737 3748
16. R.E. Carson, Y. Wu, L. Lang, Y. Ma, M.G. Der, P. Herscovitch, and W.C. Eckelman Brain uptake of the acid metabolites of F-18-labeled WAY 100635 analogs J. Cereb. Blood Flow Metab. 23 2003 249 260 (Pubitemid 36188463)
17. 1A receptors in human brain J. Nucl. Med. 48 2007 1154 1161 (Pubitemid 47052656)
18. 18F-labeled mefway, in rodents and imaging by PET in nonhuman primate J. Nucl. Med. 47 2006 1697 1706 (Pubitemid 47545037)
19. 1A receptor J. Med. Chem. 54 2011 3480 3491
20. 1A receptors: syntheses, radiosyntheses, and in vitro and in vivo evaluation Nucl. Med. Biol. 25 1998 769 776 (Pubitemid 28557103)
21. V.W. Pike PET radiotracers: crossing the blood-brain barrier and surviving metabolism Trends Pharmacol. Sci. 30 2009 431 440
22. P.E. Eaton, N. Nordari, J. Tsanaktsidis, and S.P. Upadhyaya Barton decarboxylation of cubane-1,4-dicarboxylic acid: optimized procedures for cubanecarboxylic acid and cubane Synthesis 1995 501 502
23. J.D. Roberts, W.T. Moreland, and W. Frazer Synthesis of some 4-substituted bicyclo[2.2.2]octane-1-carboxylic acids J. Am. Chem. Soc. 75 1953 637 640
24. L.G. Humber, G. Myers, L. Hawkins, C. Schmidt, and M. Boulerice Agents affecting lipid metabolism XIII. The synthesis of 1,4-disubstituted bicyclo[2.2.2]octane derivatives Can. J. Chem. 42 1964 2852 2860
25. R. Mozingo, H. Adkins, and L. Richards Catalyst, Raney Nickel, W-2 Org. Syn. Coll. 3 1955 181 21 (1941) 15
26. C.N. Sukenik, S.S. Wang, and K. Kumar Synthesis, characterization, and chemistry of bridgehead-functionalized bicyclo[2.2.2]octanes: reactions at neopentyl sites J. Org. Chem. 49 1984 665 670
27. E.W. Della, and J. Tsanaktsidis Synthesis of bridgehead-bridgehead substituted bicycloalkanes Aust. J. Chem. 38 1985 1705 1718
28. R. Priefer, P.G. Farrell, and D.N. Harpp Effective synthetic routes to cubylcarbinol derivatives Synthesis 2002 2671 2673 (Pubitemid 36034424)
29. W.J. Middleton New fluorinating reagents. Dialkylaminosulfur fluorides J. Org. Chem. 40 1975 574 578
30. M. Aleksandrov, G.I. Danilenko, and L.M. Yagupol'skii Fluorine derivatives of adamantane J. Org. Chem. USSR 9 1973 976 977
31. J. Christopher Mc Williams, F.J. Fleitz, N. Zheng, and D. Armstrong Preparation of n-butyl-4-chlorophenyl sulfide Org. Syn. Coll. 10 2004 147 79 (2002) 43
32. P. Bosch, F. Camps, and E. Chamorro Trtrabutylammonuim bifluoride: a versatile and efficient fluorinating agent Tetrahedron Lett. 28 1987 4733 4736
33. C.R. Davis, D.C. Swenson, and D.J. Burton Tetramethyl 1,1,4,4-cyclohexanetetacarboxylate: preparation and conversion to key precursors of fluorinated, stereochemically defined cyclohexanes J. Org. Chem. 58 1993 6843 6850
34. 2α methyl ester J. Org. Chem. 48 1983 3497 3502 (Pubitemid 14186945)
35. A. Ricci, A. Degl'innocenti, M. Fiorenza, M. Taddei, M.A. Spartera, and D.R.M. Walton Fluoride ion induced reactions of organosilanes with electrophiles Tetrahedron Lett. 23 1982 577 578
36. D.W. Kim, H.J. Jeong, S.T. Lim, and M.H. Sohn Tetrabutylammonium tetra-butanol coordinated fluoride as a facile fluoride source Angew. Chem. Int. Ed. 47 2008 8404 8406
37. D.W. Kim, H.J. Jeong, S.T. Lim, M.H. Sohn, J.A. Katzenellenbogen, and D.Y. Chi Facile nucleophilic fluorination reactions using tert-alcohol as reaction medium: significantly enhanced reactivity of alkali metal fluorides and improved selectivity J. Org. Chem. 73 2008 957 962 (Pubitemid 351198739)
38. I.A. Cliffe, H.L. Mansell. European Patent nr. 0 512 755 A2, 1993.
39. D. Lednicer, and M.F. Grostic Selective demethylation of deoxyanision. Mass spectra of the products J. Org. Chem. 32 1967 3251 3253
40. 50) of an enzymatic reaction Biochem. Pharmacol. 22 1973 3099 3108